Background Hypertension is a multigenetic inheritable disease.Gene therapy with long-term effects and less side effects by regulating gene expression has been shown to be a potential and exciting prospect. Objective To investigate the effects of RNA interference(RNAi)targeting angiotensin-converting enzyme(ACE)on the blood pressure and ACE expression in kidney of spontaneously hypertensive rats(SHR).Methods SHR were randomly to receive placebo(n=12)or control adenovirus Ad5-EGFP)or a single injection of recombinant adenovi- ral vectors,Ad5-EGFP-ACE-shRNA(n=12,iv).Normotensive Wistar-Kyoto rats(WKY)were served as normal control group.SBP was measured before and after the intervention.Aorta,lung,myocardium and kidney were studied using fluorescence microscope to identify the sites of Ad5-EGFP-ACE-shRNA.Expressions of ACE mRNA and protein in kidney were evaluated by RT-PCR and Western blot.Results SBP of the treat group was effectively reduced by 19.0?3.2 mmHg at the 3rd day,and 22.1?3.3 mmHg at the 13th day of the experiment.The anti- hypertensive effect significant remained at least for 14 days.On the contrary,increase in BP was shown in placebo and the adenovirus control group.Compared with placebo or adenovirus control rats,ACE mRNA expression level in kidney of the treated rats was lower by 61.1% and 62.3% respectively,with ACE protein expression level lower- ing by 56.2% and 53.30% as well(ail P0.05). Conclusion RNA interference targeting ACE gene inhibits the expressions of ACE mRNA and protein.A single dose injection resulted in a prolonged decrease in BP.The evidence of strong antihypertensive effect by genetic therapy justifies efforts for further investigation.

Abstract: Objective　To investigate the clinical and laboratory characteristics of pulmonary infection caused by Nocardia otitidiscaviarum. Methods　The clinical data of a patient with pulmonary infection caused by Nocardia otitidiscaviarum were reported, and the clinical characteristics, laboratory characteristics and drug sensitivity of pulmonary infection caused by Nocardia otitidiscaviarum were summarized in combination with the relevant literature at home and abroad from January 2010 to December 2022. Results　A 67-year-old female patient was admitted to the hospital on June 30, 2020 because of "repeated chest tightness and shortness of breath for 3 years, aggravated cough, expectoration and fever". The sputum, alveolar lavage fluid and blood of the patient were collected for culture, and the detected pathogenic bacteria were identified. There are pathogenic bacteria growing in sputum and alveolar lavage fluid, which are identified as Nocardia otitidiscaviarum by Autof ms mass spectrometer. According to the results of pathogenic bacteria and the patient's condition, meropenem combined with compound sulfamethoxazole tablets were given anti-infection treatment, and the patient's condition improved and discharged. Conclusion　The clinical manifestations and imaging features of nocardiosis are lack of specificity, and are prone to misdiagnosis and missed diagnosis. Etiology is the key to disease diagnosis, and clinical examination and culture should be conducted in time.

The dry seeds of Cassia obtusifolia were carried by the "ShenZhou 8" satellite and sowed after landing. Based on our pri- or study on SP1, the characteristics of plants growth, physiological index and content of effective components were examined. The results showed that the QC10, QC29 strains matured 5 d earlier compared with control. The plant height, across diameter and ground diameter of QC10, QC29, QC46 strains was superior to the control at whole growth period. The branch number increased ranging from 4 to 11 and the number of pods reached 321, 313,281, respectively, which was dramatically higher than the control (246). The yield of QC10, QC29, QC46 strains increased noticeably from 31.4 to 63.2 g. The 1000-seed-weight of QC10, QC29, QC46 strains was 25.86, 25.88, 24.06 g, while the control was 23.69 g. Compared to the control, the mass fraction of chlorophyll was enhanced 1.098, 1.016, 0.297 mg. There was no significant difference in aurantio-obtusin and chrysophanol content of seeds. Through two years research, three high-yield mutant strains were obtained. This study indicates that spaceflight-induced mutants could provide new germplasm for C. obtusifolia breeding and offers the theoretical basis for further utilization of spaceflight-induced mutation to breed high-quality C. obtusifolia strains.
Cassia ; chemistry ; genetics ; growth & development ; Mutation ; Space Flight

Antigens, Neoplasm ; metabolism ; Antigens, Surface ; metabolism ; Colorectal Neoplasms ; immunology ; pathology ; Humans ; Prognosis ; Trophoblasts ; immunology

OBJECTIVETo investigate the effects of RNA interference (RNAi) targeting angiotensin II Type 1 receptor (ATlR) and angiotensin-converting enzyme (ACE) on blood pressure and myocardial remodeling in spontaneous hypertensive rats (SHRs).

METHODSSaline (control), adenovirus (Ad5) and recombinant adenoviral vectors (Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA expressing ACE, AT1R, ACE and AT1R gene-specific shRNA, respectively) were randomly administered by caudal intravasation to SHRs (n = 12 each group) at day 1 and 17. Normotensive Wistar-Kyoto rats (WKY) served as normal controls. Systolic blood pressure (SBP) of the caudal artery was measured daily. Expression of ACE and AT1R at mRNA levels in ventricle and aorta were evaluated by fluorescence quantitative PCR. Angiotension II serum concentration was measured by ELISA at day 3 (n = 6 each group). The ratio of left ventricular to body weight (LVW/BW) and myocardial collagen content were measured, myocardial ultrastructure observed under transmission electron microscope at the study end.

RESULTSThe caudal artery pressure of saline and Ad5 group was equally increased by about 26 mm Hg(1 mm Hg = 0.133 kPa) compared to baseline (both P < 0.05). Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA injection significantly reduced SBP (-24 mm Hg, -22 mm Hg and -26 mm Hg respectively, all P < 0.05 vs. baseline) and the antihypertensive effect could last at least 15 days post each injection. SBP was not affected by saline and Ad5 injections. ACE and AT1 mRNA expressions at ventricle and aorta were significantly decreased in Ad5-ACE-shRNA, Ad5-ACE-AT1R-shRNA and Ad5-AT1R-shRNA, Ad5-ACE-AT1R-shRNA treated SHRs compared to those in saline and Ad5 groups (all P < 0.05) and was comparable to that in WKY group (P > 0.05). The LVW/BW ratio [(2.22 +/- 0.18) microg/mg, (2.23 +/- 0.19) microg/mg, (2.17 +/- 0.16) microg/mg] and myocardial collagen content [(1.291 +/- 0.019) microg/mg, (1.298 +/- 0.019) microg/mg, (1.276 +/- 0.019) microg/mg] in Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA treated SHRs were also significantly lower than those in saline treated [(3.23 +/- 0.13) microg/mg and(1.683 +/- 0.013) microg/mg, both P < 0.05] and Ad5 treated SHRs [(3.25 +/- 0.12) microg/mg and(1.693 +/- 0.013) microg/mg, both P < 0.05], but still higher than those of WKY group [(2.06 +/- 0.12) microg/mg and (1.258 +/- 0.019) microg/mg, both P < 0.05]. Myocardial ultrastructure was also significantly improved in all SHRs underwent RNAi treatments compared to saline and Ad5 treated SHRs.

CONCLUSIONRNAi targeting ACE and AT1R gene significantly inhibited myocardial and aortic ACE and AT1R mRNA expressions and resulted in prolonged antihypertensive effects and myocardial ultrastructure improvements in SHRsl. The RNAi technology may be a potential new strategy of gene therapy for hypertension.

Animals ; Blood Pressure ; Gene Silencing ; Heart Rate ; Hypertension ; genetics ; physiopathology ; Male ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; RNA Interference ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Ventricular Remodeling

OBJECTIVETo determine the efficacy of the plant-derived bioflavonoid, quercetin, for treating nonalcoholic fatty liver disease (NAFLD) by using a rat model, and to investigate the molecular mechanism underlying its therapeutic effects.

METHODSOne-hundred Sprague-Dawley rats were randomly assigned into the normal control group (normal group), untreated NAFLD model control group (model group), 75 mg/kg/day quercetin treatment group (low-dose group), and 300 mg/kg/day quercetin treatment group (high-dose group). The NAFLD rat model was established by providing four weeks of a high-fat diet; the normal group received normal rat chow diet. The quercetin treatments were administered for eight weeks after model establishment and control groups received simultaneous gavages of isotonic saline, with continuation of the respective diets. At the end of the eight weeks (experimental week 12), the rats were sacrificed for liver and serum collection. Intergroup differences in liver index, fasting blood glucose (FBG), triglycerides (TG), interleukin (IL)-18, IL-10, malondialdehyde (MDA), and histopathological features were assessed by independent samples t-test (normal vs. model), one-way ANOVA (model vs. treatments), and least significant difference t-test (pairwise comparisons); correlations were assessed by Pearson's correlation coefficient.

RESULTSCompared with the normal group, the model group showed significantly higher liver index (t=-2.327), FBG (t=-3.482), TG (t=-0.302), and serum IL-18 (t=-2.704) (all P less than 0.05), but significantly lower IL-10 (t=2.622, P less than 0.05); the MDA level was also higher in the model group, but the difference was not significant (t=-1.083, P less than 0.05). Livers from the model group showed obvious histological features of inflammation (lymphocyte and neutrophil infiltration) and steatosis (cytoplasmic lipid droplets). Inflammation was positively correlated with IL-18 (P less than 0.05), but negatively correlated with IL-10 (P less than 0.05), while steatosis was negatively correlated with IL-10 (P less than 0.05). Compared to the model group, quercetin treatment (both low- and high-dose) led to significant decreases in the liver index, FBG and IL-18 (all, P less than 0.01), and significant increase in IL-10 (P less than 0.05); however, the changes in liver index, FBG and IL-10 were not significantly different between the low- and high-dose treatment groups, but the high-dose of quercetin did induce a significantly greater decrease in IL-18 than the low-dose (P less than 0.05).

CONCLUSIONNAFLD rats have higher serum levels of IL-18 but lower levels of IL-10 than their healthy counterparts, and these differential cytokine expressions may be related to liver inflammation and steatosis. Quercetin treatment may help to delay the progression of NAFLD, possibly by adjusting the balance of inflammatory cytokines.

Animals ; Fatty Liver ; blood ; drug therapy ; Interleukin-10 ; blood ; Interleukin-18 ; blood ; Male ; Non-alcoholic Fatty Liver Disease ; Quercetin ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of quercetin on serum levels of resistin and interleukin (IL)-18 and incidence of insulin resistance (IR) in nonalcoholic fatty liver disease (NAFLD) using a rat model.

METHODSNAFLD was induced in Sprague-Dawley rats by administering a high-fat diet for four weeks. The model rats were then treated with quercetin (oral gavage administration; low dose group: 75 mg/kg/day, high dose group: 300 mg/kg/day) for eight weeks. Untreated model rats served as controls. Serum levels of resistin, triglyceride (TG), IL-18, fasting plasma glucose (FPG), fasting insulin (FINS), and malondialdehyde (MDA) were measured by standard biochemical assays before and after the quercetin administration. In addition, the insulin resistance index (HOMA-IR) was calculated and pathological changes in liver were observed by histological analysis.

RESULTSCompared to the untreated model rats, the quercetin treated model rats showed significantly lower serum resistin (5.98 vs. 2.70), serum IL-18 (10.93 vs. 8.21), FPG (7.45 vs. 4.99), FINS (12.69 vs. 8.59), and HOMA-IR (4.22 vs. 1.87) (all P less than 0.01). Compared to the untreated model group, the high dose group showed significantly lower TG (t = 4.70) and MDA (t = 5.14) (both P less than 0.01). Serum levels of resistin and IL-18, and levels of TG, FPG and FINS were found to be positively correlated with HOMA-IR and the degree of liver disease (r more than 0, all P less than 0.05). The degree of degeneration was decreased in accordance with the dosages of quercetin, as compared to the untreated model group (U = 4.41 and 2.19, both P less than 0.05), and the pathological degree was less extensive in the high dose group than in the low dose group (U = 2.44, P less than 0.01).

CONCLUSIONQuercetin treatment reduces levels of inflammatory cytokines and improves lipid peroxidation and IR in NAFLD rats, and its beneficial effects appear to increase with higher dosage.

Animals ; Insulin Resistance ; Interleukin-18 ; blood ; Non-alcoholic Fatty Liver Disease ; Quercetin ; Rats ; Rats, Sprague-Dawley ; Resistin

OBJECTIVETo investigate the effects of RNA interference (RNAi) targeting angiotensin-converting enzyme (ACE) on the blood pressure and myocardial remodeling in spontaneously hypertensive rats (SHRs).

METHODSSaline (control), adenovirus (Ad5) and recombinant adenoviral vectors (Ad5-ACE-shRNA expressing ACE gene-specific shRN) were randomly administered by caudal intravasation to SHRs (n = 12 each group) at day 1 and day 16. Normotensive Wistar-Kyoto rats (WKY) served as normal controls. Systolic blood pressure (SBP) of the caudal artery was measured daily. Expressions of ACE at mRNA and protein levels in myocardium and aorta were evaluated by RT-PCR and Western blot respectively, ACE serum concentration was measured by ELISA at day 3 (n = 6 each group). The ratio of left ventricular to body weight (LVW/BW), myocardial collagen content were measured and myocardial ultrastructure observed under transmission electron microscope at the study end.

RESULTSAd5-ACE-shRNA injection significantly reduced SBP (-22 mm Hg, 1 mm Hg = 0.133 kPa) and the antihypertensive effect could last at least 14 days post each injection. SBP was not affected by saline and Ad5 injections. ACE expressions at mRNA and protein levels at myocardium and aorta as well as serum ACE were significantly decreased in Ad5-ACE-shRNA treated SHRs compared to that in saline and Ad5 groups (all P < 0.05) and was comparable to that in WKY group (P > 0.05). The LVW/BW ratio (2.24 +/- 0.19) and myocardial collagen content [(1.283 +/- 0.019) microg/mg] in Ad5-ACE-shRNA treated SHRs were also significantly lower than those in saline treated [3.21 +/- 0.13 and (1.686 +/- 0.013) microg/mg, both P < 0.05] and Ad5 treated SHRs [3.13 +/- 0.12, (1.682 +/- 0.009) microg/mg, both P < 0.05] but still higher than those of WKY group [2.06 +/- 0.11, (1.257 +/- 0.019) microg/mg, both P < 0.05]. Myocardial ultrastructure was also significantly improved in Ad5-ACE-shRNA treated SHRs compared to saline and Ad5 treated SHRs.

CONCLUSIONRNAi targeting ACE gene significantly inhibited the expressions of ACE at mRNA and protein levels and resulted in prolonged antihypertensive effects and myocardial ultrastructure improvements in this SHR model.

Animals ; Blood Pressure ; Disease Models, Animal ; Heart Rate ; Hypertension ; genetics ; physiopathology ; Male ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Ventricular Remodeling

Objective To explore the establishment of a rat model of acute radiation-induced liver injury and sig-nificance of the dynamic changes of TGF-β1 expression.Methods Forty healthy 6-week old male SD rats were randomly divided into model group (n=30) and control group (n=10).The right liver of rats in the model group was given a single dose of 25 Gy 6 MV X-ray irradiation.Histopathological examination using HE staining and transmission electron microsco-py were conducted to observe the liver pathological changes in rats at 3, 5, and 10 days after irradiation, serum TGF-β1 was detected, and relevant indicators of liver function ( ALT, AST, ALP) were determined.Statistical analysis was per-formed using SPSS 17.0 software.Results At 3, 5 and 10 days after irradiation, early pathological changes in the liver cells were observed by electron microscopy, the expression of TGF-β1 was gradually increased with the time prolongation, and significant differences were found between the model group and the control group at different time points (P<0.05). The light microscopic observation of liver tissues did not show significant differences between the control group and model group.The liver ALT, AST, ALP at different time points did not show significant differences between the two groups ( P>0.05).Conclusion Electron microscopy can be used to evaluate the early changes of radiation-induced liver injury, pri-or to the alterations visible by routine light microscopy.TGF-β1 can be used to predict the degree of radiation-induced liver injury, and may be used as a sensitive serum cytokine in predicting the degree of radiation-induced acute liver injury.

OBJECTIVETo explore the effectiveness of postoperative electron beam irradiation therapy for keloid.

METHODSForty-eight patients with 65 keloid sites were treated by surgical removal and postoperative 25 Gy electron beam irradiation from 1994 to 2002 and followed for over eighteen months. Statistical analysis was performed and therapeutic outcome was evaluated.

RESULTSThe overall recurrence rate was 26%. Higher post-treatment recurrence rates were noted with keloid forming at infected sites and in patients with family history (47.8% and 53.3%) (P < 0.05). Meanwhile, patient age, sex, keloid size and location had no increased likehood of recurrence rate.

CONCLUSIONThe study shows that postoperative electron beam irradiation therapy is a kind of safe and effective method in inhibiting recurrence of keloid formation and eradicating it.

Adult ; Combined Modality Therapy ; Electrons ; Female ; Follow-Up Studies ; Humans ; Keloid ; radiotherapy ; surgery ; Male ; Postoperative Care ; Recurrence ; Treatment Outcome